Structure of calcineurin in complex with PVIVIT peptide: Portrait of a low-affinity signalling interaction
Structure of calcineurin in complex with PVIVIT peptide: Portrait of a low-affinity signalling interaction
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DOI：
10.1016/j.jmb.2007.04.032
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发表时间：
2007-06-22
影响因子：
5.6
通讯作者：
Hogan, Patrick G.
中科院分区：
文献类型：
--
作者：
Li, Huiming;Zhang, Lan;Hogan, Patrick G.
钙调神经磷酸酶识别多种底物，控制真核细胞的多种发育和生理途径。转录因子NFAT和某些其他钙调磷酸酶底物的去磷酸化依赖于钙调磷酸酶在PxIxIT共有位点的对接。我们在这里描述的结构基础识别的PxIxIT序列的钙调神经磷酸酶。我们证明了高亲和力肽配体PVIVIT作为β链添加到钙调神经磷酸酶β折叠的边缘;含有PxIxIT共有序列的短肽片段足以用于钙调神经磷酸酶-底物对接;并且PxIxIT核心内的序列变化在1 μ M至1 mM的生理范围内调节相互作用的Kd。钙调磷酸酶可以适应多种底物，因为识别仅需要PxIxIT序列，并且因为核心PxIxIT序列内的变化可以微调亲和力以匹配各个底物的生理信号传导要求。(C)2007爱思唯尔有限公司版权所有。
The protein phosphatase calcineurin recognizes a wide assortment of substrates and controls diverse developmental and physiological pathways in eukaryotic cells. Dephosphorylation of the transcription factor NFAT and certain other calcineurin substrates depends on docking of calcineurin at a PxIxIT consensus site. We describe here the structural basis for recognition of the PxIxIT sequence by calcineurin. We demonstrate that the high-affinity peptide ligand PVIVIT adds as a beta-strand to the edge of a beta-sheet of calcineurin; that short peptide segments containing the PxIxIT consensus sequence suffice for calcineurin-substrate docking; and that sequence variations within the PxIxIT core modulate the Kd of the interaction within the physiological range 1 mu M to 1 mM. Calcineurin can adapt to a wide variety of substrates, because recognition requires only a PxIxIT sequence and because variation within the core PxIxIT sequence can fine-tune the affinity to match the physiological signalling requirements of individual substrates. (C) 2007 Elsevier Ltd. All rights reserved.